Exam 4 Flashcards
(261 cards)
1
Q
Empagliflozin non-diabetes FDA indications
A
Reduce risk of CV death (EMPA-REG trial)
2
Q
Canagliflozin non-diabetes FDA indications
A
Reduce risk of MACE
Reduce risk of end-stage kidney disease, doubling of SCr, CV death, hospitalization for HF in patients with T2DM with neuropathy and albuminuria
CANVAS trial
3
Q
Dapagliflozin non-diabetes FDA indications
A
Reduce risk of HF hospitalization in patients with T2DM and CVD or multiple CVD risk factors
Tx of heart failure with reduced ejection fraction in adults w/ or w/o T2DM
DECLARE-TIMI 58
4
Q
Non-diabetes FDA indications for liraglutide, dulaglutide, and semaglutide
A
Reduce risk of MACE
5
Q
Sulfonylurea MOA
A
sulfonylureas bind to the SUR1 receptor on pancreatic beta cells without the presence of glucose or ATP. This closes the ATP-dependent calcium channel opens the calcium channel and triggers insulin release
6
Q
Sulfonylurea insulin effect
A
Mixed effect on FPB and PPG
7
Q
Glipizide Class: Brand: Dose: Duration of action: Active metabolites?
A
Class: Sulfonylurea Brand: Glucotrol Dose: 5-40mg QD-BID Duration of action: Up to 20 hours Active metabolites? No
8
Q
Glipizide ER Class: Brand: Dose: Duration of action: Active metabolites?
A
Class: Sulfonylurea Brand: Glucotrol XL Dose:5-20mg QD Duration of action: 24 hours Active metabolites? No
9
Q
Glimepiride Class: Brand: Dose: Duration of action: Active metabolites?
A
Class: Sulfonylurea Brand: Amaryl Dose: 1-8mg QD Duration of action: 24 hours Active metabolites? No
10
Q
Why are most sulfonylureas QD?
A
Because most of them have a 24 hour onset of action
Sometimes dosed BID because this decreases the peak effect which decreases the risk of hypoglycemia
11
Q
Sulfonylureas AE
A
Hypoglycemia Weight Gain (sulfonylureas promote the release of insulin which is an anabolic hormone and it builds up fat and protein and allows for more glucose to enter the cells)
Less common: rash, photosensitivity, dyspepsia, nausea, HA
12
Q
Sulfonylureas contraindications
A
Hypersensitivity
DKA
Type 1 Diabetes
H/O allergic reaction to sulfonamide derivatives (glimepiride)
Concomitant administration of bosentan (glyburide)
13
Q
Sulfonylureas advantages/disandvantages
A
Advantages- quick onset, high initial response rate, inexpensive
Disadvantages- hypoglycemia, weight gain, high secondary failure rate (5-10%/year)
14
Q
Sulfonylureas DDI
A
CYP2C9
15
Q
Do you titrate sulfonylureas?
A
Yes, to minimize the AE if hypoglycemia and to reach target dose
16
Q
Why is there a high secondary failure rate with sulfonylureas?
A
Because their activity depends on active, functional beta cells and we lose beta cell mass and function at a rate of 5-10%/year
17
Q
Meglitinides (Glinides) MOA
A
Similar MOA to sulfonylurea, the binding site is adjacent.
Difference- requires presence of glucose so hypoglycemia is less common
18
Q
Meglitinides (Glinides) medications and where they effect BG
A
Repaglinide, Nateglinide- both rarely used because they are dosed TID before meals so adherence is poor.
Requires glucose so they effect the PPG
19
Q
Meglitinides (Glinides) adverse effects and contraindications
A
AE: hypoglycemia and weight gain
Contraindications: hypersensitivity, DKA, T1DM, Repaglinide with gemfibrozil
20
Q
Meglitinides (glinides) advantages/disadavantages and metabolism
A
Advantages- Rapid onset of action, less AE than sulfonylureas, postprandial glucose
Disadvantages- hypoglycemia, weight gain, secondary failure (MOA depends on a functional beta cell), and TID dosing
Metabolism- CYP2C8 (DDI with repaglinide and TMP)
21
Q
Biguanide (metformin) MOA
A
Primary effect on the liver, it inhibits gluconeogenesis (production of glucose from noncarbohydrate precursors)
Secondarily causes improvement on peripheral insulin resistance
22
Q
Metformin dose/brand name
A
Glucophage or Glucophage XR
Dose titration to decrease the AE of diarrhea until maximum dose of 2,550mg/day.
Titrate by increments of 500mg at biggest meal of the day
Even glucophage XR is split into BID dosing to minimize peak effects and decrease AE
23
Q
What BG does metformin effect?
A
FPG because the liver is the primary source of glucose in the fasting state
24
Q
Metformin AE
A
Common: N/V/D (Diarrhea most common), these effects are transient and will go away with continued use
Uncommon: macrocytic anemia
25
Metformin contraindications and BBW
Hypersensitivity
eGFR <30mL/min
Active chronic metabolic acidosis
BBW- lactic acidosis
26
Metformin warnings/precautions
Starting metformin in patients with a eGFR 30-45mL/min is not recommended
IV contrast-induced nephropathy
Hypoxic states (renal failure, liver failure, HF, pulmonary failure increase lactate)
Severe hepatic/pulmonary disease
27
Cori cycle
Causes an increase in lactate through backup processes. In anaerobic conditions we could see an increase in lactate, contributing to metformin- induced lactic acidosis
28
Metformin advantages/disadvantages and DDI
Advantages- no hypoglycemia as monotherapy (it does not increase the release of insulin), weight neutral or loss, high initial response rate, positive lipid effects (decrease LDL, TG and increases HDL), inexpensive
Disadvantages- GI AE (take WF to help)
DDI-cimetidine
29
Thiazolidinediones MOA
Increases insulin sensitivity
Secondarily decreases hepatic glucose production
PPAR-y agonist
30
Thiazolidinediones adverse effects
```
Weight gain (glucose enters cell)
Fluid retention (increased incidence with insulin)
HF exacerbation
Fractures
Hepatotoxicity
Bladder cancer
Macular edema
```
31
Pioglitazone
Thiazolidinedione
15-45mg QD titrated to therapeutic response
Delayed onset of action so the maximal effect is seen in 8-12 weeks
Mixed effect, but primarily FPG
32
Thiazolidinediones contraindications
NYHA Class III and IV HF
33
Thiazolidinedione advantages and disadvantages
Advantages- No hypoglycemia as monotherapy, favorable lipid effects (increase HDL, decrease TG), can use in renal in sufficiency
Disadvantages- delayed onset of action, several potential AE, recommend LFT monitoring
34
Thiazolidinedione DDI
Gemfibrozil w/ pioglitazone
| Max dose of pioglitazone 15mg/day
35
alpha-glucosidase inhibitors MOA
Prevents breakdown of complex carbohydrates into glucose, delaying and reducing post-meal carb absorption and post prandial BG rise.
Must take WF since it inhibits the breakdown of complex carbs.
36
alpha-glucosidase inhibitors meds and glucose effect
acarbose and miglitol
Both dose titrated
Effect on PPG
37
alpha-glucosidase inhibitors adverse effects
Common (directly related to carbs not be digested)- flatulence, abdominal discomfort, diarrhea
Rare- LFT elevation (acarbose)
38
alpha-glucosidase inhibitors contraindications and warnings/precautions
Contraindications- hypersensitivity, DKA, cirrhosis, IBD, colonic ulceration, intestinal obstruction
warnings/precautions- SCr >2mg/dL
39
alpha-glucosidase inhibitors advantages/disadvantages
Advantages- no hypoglycemia as monotherapy, weight neutral
| Disadvantages- modest efficacy, poorly tolerated GI AE, slow titration, multiple doses/day so poor adherence
40
DPP-4 inhibitors MOA
DPP4 inactivates or breaks down the incretin hormones (GLP-1 and GIP-1)
The incretin hormones come from the intestines (L cells) and you see a bigger rise after a meal.
In T2DM, you have a decrease in incretin hormones and DPP-4 inhibitors prevent the breakdown of your bodies own GLP-1
41
What does GLP-1 do?
Gut- delays gastric emptying
Liver- suppresses glucagon secretion
Pancreas- increases insulin release
1- 1 brain- suppresses appetites, increases satiety
42
What BG do DPP-4 inhibitors effect?
PPG because they only work in the presence of glucose. DPP-4 inhibitors are only around when GLP-1 is around which is when you're eating
43
```
Sitagliptin
Class:
Brand:
Dose:
A1C lowering monotherapy:
A1C lowering combo therapy:
Renal dosing:
```
```
Class: DPP-4 inhibitor
Brand: Januvia
Dose: 100mgQD
A1C lowering monotherapy- 0.6%
A1C lowering combo therapy- 0.7%
Renal dosing:
50mg QD when CrCl 30-50mL/min
25mg/day when CrCl <30mL/min
```
44
```
Linagliptin
Class:
Brand:
Dose:
A1C lowering monotherapy:
A1C lowering combo therapy:
Renal dosing:
```
```
Class: DPP-4 inhibitor
Brand: Tradjenta
Dose: 5mg QD
A1C lowering monotherapy: 0.4%
A1C lowering combo therapy: 0.7%
Renal dosing: N/A
```
45
DPP-4 inhibitors AE and drug interactions
AE- nasopharyngitis (runny nose), URI, HA.
Very well tolerated
DDI- CYP3A4
46
DPP-4 inhibitors contraindications, warnings and precautions
Contraindications- hypersensitivity
| Warnings/Precautions- pancreatitis, HF, arthralgia (goes away if you D/C)
47
DPP-4 inhibitors advantages/disadvantages
Advantages- No hypoglycemia as monotherapy, weight neutral
| Disadvantages- expensive
48
Bile acid sequestrants MOA and medication
Inhibits bile acid reabsorption leading to a decrease in hepatic glucose production
Colesevelam- tk with food
49
Bile acid sequestrants AE, contraindications, DDI
AE- constipation
contraindications (all because of constipation)- H/O bowel obstruction, TG >500mg/dL, H/O TG-induced pancreatitis
DDI- separate other drugs by 4 hours
50
Bile acid sequestrants advantages/disadvantages
Advantages- No hypoglycemia as monotherapy, LDL lowering of 15-18%, may increase metformin tolerability
Disadvantages- Modest A1C lowering, high pill burden, may raise TG
51
Dopamine agonist (Bromocriptine) MOA, effects which BG
Unknown
Increases EPI/NE to improve insulin sensitivity in the liver
Effect PPG
52
Dopamine agonists (Bromocriptine) AE and contraindications
AE- GI and CNS (N/V, asthenia, constipation, dizziness, somnolence)
Contraindications- hypersensitivity to ergot derivative, lactation, syncopal migraines
53
Dopamine agonists (bromocriptine) advantages/ disadvantages/ DDI
Advantages- unique MOA
Disadvantages- modest efficacy, AE, cost
DDI- CYP3A4, protein-binding, drug-disease
54
SGLT2 inhibitors MOA
In T2DM, you see an upregulation of SGLT2. SGLT2 inhibitors inhibit the reabsorption of glucose and glucose gets eliminated in the urine
55
SGLT2 effects which BG?
It effects both FPG and PPG and has a low risk of hypoglycemia
56
Canagliflozin
Brand
Dosing Renal dosing
Brand- Invokana
Dosing- 100-200mg daily (can titrate up from lower dose or start from higher one)
Renal dosing- Not recommended if GFR <45
If GRF 30-45 +UACR >300= 100mg daily
57
EMPA-REG outcome
Empagliflozin gets approved for reduce the risk of CV events
58
CANVAS trial
Canagliflozin gets approved for reduce risk of CV events
59
DECLARE-TIMI 58
Dapagliflozin gets approved to reduce risk of HF hospitalization in patients with T2DM and CVD or multiple CVD risk factors
60
VERTIS CV
Ertugliflozin has no heart benefits
61
SGLT2 inhibitors AE
```
Hypotension (bc of water loss)
Hyperkalemia
Genital mycotic infections
UTI
Increased urination
Euglycemic DKA (why we shouldnt use in T1)
Bone fractures (canagliflozin)
AKI
Bladder cancer (dapagliflozin)
Leg/foot amputations
```
62
SGLT2 inhibitors contraindications
Hypersensitivity
Severe renal impairment
ESRD
Dialysis
63
SGLT-2 inhibitors advantages/disadvantages
Advantages- unique MOA, no hypoglycemia as monotherapy, weight loss, decrease in SBP
Disadvantages- AE, cost
64
Warning for all SGLT2 inhibitors
Necrotizing fasciitis of the perineum (fourniers gangrene), rare-life threatening bacterial infection
65
How do SGLT2 inhibitors help with HF?
Normally, the SGLT2 inhibitor causes Na and Glucose to be reabsorbed and K to be wasted in the urine.
With a SGLT2 inhibitor, Na, glucose, and water are all wasted in urine.
Consequently, hyperkalemia is possible bc it is being retained
66
Euglycemic DKA
When BG is normal but a patient still has DKA
when insulin decreases, lipolysis and glucagon increases, this leads to FFA formation which gets broken down into ketones
Look for N/V and abdominal pain
67
CREDENCE
Canagliflozin
FDA approval to reduce risk of ESRD, double of SCr, CV death, and hospitalization in HF for pts with T2DM and diabetic nephropathy with albuminuria
68
DAPA-CKD
Dapagliflozin shown to have positive benefits on CKD progression
69
DAPA- HF
Dapagliflozin
50% pts with diabetes and 50% w/o
Showed benefit in patients with HF
70
EMPEROR-reduced
Empagliflozin
| statistically significant results in HF and decrease risk of CV death
71
How do SGLT2 inhibitors regulate tubuloglomerular filtration?
Normally, the SGLT2 channel reabsorbs Na and glucose and the rest of the Na gets sent to macula densa which causes the macula densa to sense Na.
In T2DM, there is a hyperfiltration that causes more glucose to be reabsorbed so there is less Na in the macula densa. This tells the body to filter faster causing a progression of CKD.
SGLT2 inhibitors cause more Na to be sent to the macula densa which regulates tubuloglomerular filtration
72
Amylin analog MOA, drug, BG effects
MOA- amylin is cosecreted with insulin in the beta cell in normal people
Amylin analogs cause synthetic amylin to be secreted which suppresses high postprandial glucagon secretion, increases satiety, and slows gastric emptying
Drug- Pramlintide -for type 1 and 2 DM (Different doses)
Effects PPG so must be administered with meals (lower dose of meal time insulin
73
Amylin analog adverse effects, contraindications, and warnings/precautions
Adverse effects- N/V, hypoglycemia with insulin (BBW)
Contraindications- hypersensitivity, gastroparesis, unawareness of hypoglycemia
Warnings/precautions- A1C >9%, patients unwilling to SMBG
74
Amylin analog advantages/disadvantages
Advantages- weight loss
| Disadvantages- additional injections, may reduce rate and absorption of drugs because of delayed gastric emptying, GI AE
75
GLP-1 receptor agonists MOA
Synthetic analog of GLP-1
GLP-1 decreases gastric emptying, decreases glucose production, causes the pancreas to release insulin, and increases satiety
Glucose dependent
76
```
Liraglutide
Class
Brand
Dosing
Administration
Delivery
Storage
Renal dosing
```
```
Liraglutide
Class- GLP-1 receptor agonist
Brand- Victoza
Dosing- 0.6mg SQ daily, titrate weekly to 1.2mg and 1.8mg if tolerated
Administration- independent of meals and time of day
Delivery- Pen
Storage- Room temp for 30 days
Renal dosing- NA
```
77
Which GLP1 receptor agonists do you have to renal dose?
Exenatide and Exenatide XR
| Not recommended with CrCl <30
78
Lixisenatide (Adlyxin)
ELIXA trial- neutral effect on CV outcomes
| Non-human based GLP1 receptor agonists
79
Semaglutide (Ozempic)
Titrated with 3 doses, first therapeutic dose at 0.5
GLP1 receptor agonist, administor any time of the day with or without meals
Long carbon fatty acid chain is why it has weekly doses
80
Oral semaglutide
Only oral GLP1 agonist
Rybelsus
PIONEER 6- neutral effect of CV outcomes
co-formulated with SNAC so that the medication gets attached to one area of the stomach
Have to take 30 minutes before eating, drinking, or taking any other medications. Take with no more than 120mL water
81
LEADER
Liraglutide decreases risk of major CV events
82
EXSCEL
Exenatide- no significant CV benefits
83
REWIND
Reduce risk of major CV events
| Dulaglutide
84
SUSTAIN-6
Semaglutide
| Decrease risk of CV events
85
GLP1 receptor agonists AE, contraindications, BBW
N/V/D (Nausea most common)
Injection site reactions or nodules (bydureon)
Contraindications- hypersensitivity, personal or family history of medullary thyroid carcinoma, patients with MEN 2
BBW- risk of thyroid C-cell tumors
86
GLP1 receptor agonists advantages and disadvanteges
Advantages- weight loss, convenient dosing
| Disadvantages- May reduce rate and absorption of drugs, injections/training, must stay hydrated or prerenal AKI possible
87
Xultophy
Insulin degludec and liraglutide
QD injection
Dose range 10-50
88
Soliqua
Insulin glargine and lixisenatide
| Administer 1 hr before 1st meal of day
89
Insulin pharmacology
Insulin is a protein that is made up of AA. It comes from proinsulin.
If you make insulin, you also make C-Peptide.
It is stored in crystals (hexamers around a zinc molecule) and degraded in the liver and kidneys.
Half life of 3-5 minutes
90
Rapid acting insulin
Insulin lispro (Humalog)
Insulin aspart (Novolog)
Insulin glulisine
(Admelog is similar but not approved to be bioequivalent)
-All insulin analogs , which are predictable! The have the lowest variability of absorption (5%).
Stabilized into hexamers by a cresol preservative. Rapid-acting insulin rapidly goes from hexamer to monomer form for diffusion.
Take about 15-20 minutes before a meal.
91
Fiasp
Faster acting insulin aspart
Ultra-rapid acting (has a 10 minute earlier onset of action than the rapid acting insulins)
Contains niacinamide (Vit B3 as an excipient that increases the absorption)
Inject at the start of a meal or within 20 minutes after starting a meal. Allows for more variability in timing.
92
Lyumjev
Faster acting insulin lispro
Comes in 100 and 200 units/ml
Excipients:
citrate- increases vascular permeability
Treprostinil- increases local vasodilation
Both allow for a quicker absorption
Administration- inject at the start of a meal or within 20 minutes after starting a meal
93
Inhaled insulin
Afrezza (human insulin, ultrarapid acting)
Acts more like a rapid acting analog
Indications- T1DM or T2DM adult, must be used with long-acting insulin if used in T1DM, not recommended for DKA or smokers
Contraindications- chronic lung disease, asthma, COPD
Warnings- decline in pulmonary function, lung cancer
Need to measure FEV1 and respiratory function
BBW- acute bronchospasm in patients with asthma/COPD
Meal time insulin
94
Afrezza storage
Inhaler- good for 15 days
| cartridges- good for 10 days at RT when sealed, 3 days when opened
95
Afrezza dosing
Use a 1.5x conversion
limited to 4, 8, or 12 units
You need more afrezza than your typical meal time insulin
Injected meal time insulin 5-8 units, afrezza dose 8units
96
Short-acting insulin
Regular insulin (human)
Self-aggregate in antiparallel fashion to form dimers and then stabilize around zinc ions to create hexamers
When injected it gets diluted by the interstitial fluid and goes from hexamers to dimers to monomers. It undergoes the dimer step to increase the onset of action.
Human insulin so variability in dose and PK/PD profile.
Because of the slower onset of action, must be given 30 minutes prior to a meal.
97
1st phase release of insulin
Insulin-independent GLUT2 receptor on the beta cell causes the calcium channel to open and insulin to be released.
Insulin is stored in the beta cell (this is messed up in T2DM)
98
Phase 2 release of insulin
Insulin meets the insulin receptor and undergoes a network of phosphorylation's that activate the GLUT4 (insulin dependent) receptor. GLUT4 (on muscles and adipose tissues) then accepts glucose into the cell to become metabolized
99
Where does insulin come from?
Beta cells
Synthetic insulin used to come from beef and pork sources but we dont use this anymore due to impurities
We use recombinant insulin made from bacteria and yeast
100
Human insulin vs. insulin analogs
Human insulin is any insulin, regardless of if you make it yourself, that has the same AA structure as the insulin we make in our own bodies,
Insulin analogs have AA switches that change the PK/PD effects.
101
Human insulin examples
Insulin glargine
Regular insulin
NPH
102
Insulin analogs examples
Insulin lispro
Insulin aspart
Insulin detemir
Insulin glulisine
103
Humulin R U-500
Typically reserved for patients requiring more than 200units/day of insulin which indicates insulin resistance.
Very dangerous so be extra sure that patient understands and uses correct syringe.
104
Intermediate-acting insulin
```
NPH insulin (human insulin)
Novolin R or Humulin R
Combination of insulin and protamine to increase duration of action. After injection, proteolytic tissue enzymes have to degrade protamine bound to the insulin hexamers before the insulin can be broken down into the dimer and monomer forms.
```
Insulin is cloudy due to the protein, do not shake but roll in hands
105
Long-acting insulin
Insulin glargine (Lantus) is soluble in acidic solutions so once it goes into the neutral bodies pH it precipitates into a crystalline depot. Individual insulin molecules slowly break away. Basaglar is also insulin glargine but they are not interchangeable.
Insulin detemir- self-aggregates due to albumin binding. Dose dependent profile (<0.3units/kg= BID, >0.3units/kg=QD)
Insulin degludec- multiple hexamer formation resulting in a SQ depot. It has reversible albumin binding.
106
Toujeo
Insulin glargine U-300 (concentrated long acting insulin)
Need 10% more Toujeo to meet needs, we dont know why.
1.5mL SoloStar or 3mL Max SoloStar
Indications: glycemic control in diabetes mellitus, not used for DKA
Can cause hyper or hypo glycemia with changes in insulin regimen
Only comes in a prefilled pen
107
Tresiba
Insulin degludec
U-100 or U-200 FlexTouch
Longest duration of action (42 hours). Builds into multihexamers once injected which causes this long DOA.
Dose daily at any time of the day
Allow for 3-4 days before dose increases
Allow a minimum of 8 hours between consecutive injections
108
Insulin stacking
Increases risk of hypoglycemia
We are worried about this in the shorter acting insulins
With longer acting insulin we do not worry because they reach steady state in a few days
109
Premixed insulin
Typically reserved for patients who have cost issues or will not take more than 2 injections per day.
%70/30= 70% NPH (bound to protein)/ 30% regular insulin (not bound)
Give at breakfast and dinner
110
Which insulin is given IV?
Regular insulin
111
Which insulins have a duration over 24 hours?
U-300 glargine and degludec
112
Which insulins have a duration under 5 hours?
Technosphere, glulisine, lispro, aspart
113
Which insulin has a duration between 4-6 hours?
Regular insulin
114
Which insulin has a duration between 8-12 hours?
NPH
115
Which insulins have a duration between 14-24 hours?
Detemir
| Glargine (U-100)
116
Insulin adverse effects
Hypoglycemia is the most common
Weight gain (insulin is anabolic and builds up fat and protein)
Injection site reactions (not as common)
117
Hypoglycemia
Typically BG <70mg/dL
S/S- Tremor, diaphoresis (sweating), lightheaded, HA, tachycardia, nervous/anxious, irritable, confusion, hunger, drowsiness
Use the Rule of 15 to treat hypoglycemia- consume 15g of simple carbohydrates (orange juice, glucose tablets) and retest in 15 minutes. Retest until BG is normalized.
118
Hypoglycemic unawareness
Loss of warning signs and S/S of hypoglycemia
119
What are the 5 counterregulatory hormones and what do they do?
They increase BG
| Glucagon, Epi, NE, Cortisol. GH
120
When do you start seeing severe symptoms of hypoglycemia?
BG under 40
121
Hypoglycemia level 1
Glucose 54-70mg/dL
122
Hypoglycemia Level 2
Glucose <54mg/dL
123
Hypoglycemia Level 3
A severe event characterized by altered mental and/or physical status requiring assistance.
124
Glucagon
For adults and children over 6 years old-
1mg (1mL) IM repeat in 15 minutes if needed
For children <6
-0.5mg (0.5mL) IM repeat in 15 minutes if needed
Place patient on side in position to avoid aspiration from vomit and call 911.
125
Gvoke and GvokeHypoPen
SQ preconstituted glucagon administration
For ages >2
Works like an epipen
126
Glucagon nasal powder
For ages 4 and up
127
Basal insulin
The insulin that your body produces at all times regardless of carb intake
128
Prandial insulin
The insulin that your body produces after meals
129
Treatment for T1DM
Patients should be treated with multiple daily injections
Pick either
-Basal and prandial injections
-Continuous subcutaneous insulin infusion
Most patients should be educated in matching prandial insulin dose to carbohydrate intake, premeal blood glucose, and anticipated activity.
Insulin analogs are preferred
130
Total Daily Dose
For a new diagnosis begin with 0.5units/kg/day.
This will be adjusted for patient-specific needs
Insulin needed for entire day
131
Basal-bolus dosing
Step 1:
Calculate TDD (insulin needed for entire day)
Step 2:
Split this dose in half. 50% will go to basal dose (NPH or long acting insulin) and 50% will be given before each meal (this 50% is divided by 3 and is given via rapid acting insulin or ultra rapid acting insulin)
132
Split-mixed dosing
2 injections/day
Calculate TDD and then split into 1/3rds.
2/3rds of TDD will be given in the morning to account for breakfast and lunch
1/3rd given at night to account for dinner. Less given at night to prevent hypoglycemia while sleeping.
133
Continuous subcutaneous insulin infusion
Uses rapid acting insulin
Mainly aspart (novolog) or lispro (humalog)
Typically given at the patients basal rate (0.5units/kg/hour)
134
Correction Factor
Also called insulin sensitivity
Calculated to estimate the approximate plasma glucose lowering effect of 1 unit of short-acting insulin.
Example: If you correction factor is 50 then 1 unit of insulin will lower your BG by 50mg/dL
Corrects premeal glucose
135
How do you calculate correction factor?
Regular insulin- 1500/TDD
Most common**** Rapid acting- 1700/TDD
136
How to calculate meal-time insulin doses
1.) Initial TDD is an estimate, it will be adjusted. Once we understand the patients true TDD we will move on to carb counting.
2.) 50% TDD is basal and 50% is prandial
Divide the 50% prandial insulin into 3 and give at
each meal. Calculate the correction factor for the
patient (1700/TDD) and add insulin based off of the
correction factor. Goal glycemic range is 80-
130mg/dL.
137
How do you make a correction factor scale?
Goal is 80-130mg/dL
Anything less than 80mg/dL, you subtract 1 unit from the dose.
The CF is then used to make the scale. If the correction factor was 30 then every 30 mg increase in BG you give 1 extra unit of insulin
138
Carbohydrate counting
Very effective
Use I:CHO ratio
Example- if your I:CHO ratio was 15 then 1 unit of insulin will cover 15 grams of carbs. If you are eating 30 carbs you would give 2 units of insulin.
Calculation:
Rule of 500-
500/TDD= I:CHO ratio for rapid-acting insulin
450:TDD= I:CHO ratio for regular insulin (less common)
139
Insulin management priority list
Keep BG between 80-130mg/dL
1. ) Target lows first
2. ) Look at FPG and fix next
3. ) Look for a 3-4 day pattern in the glucose log
4. ) Identify the insulin dose that is responsible for the increase or decrease in BG
5. ) Adjust this dose by 10-20%
Only adjust 1 dose at a time and then look for a new pattern.
140
Pre-breakfast BG value is caused by what?
Meal- Dinner/bedtime
Insulin-
Basal-bolus- Bedtime (long-acting)
split-mixed- (Pre-dinner NPH)
141
Pre-lunch BG value is caused by what?
Meal- Breakfast
Insulin-
Basal-bolus and split mixed- pre-breakfast insulin (rapid-acting)
142
Pre-dinner BG value is caused by what?
Meal-lunch
Basal-bolus- Pre-lunch dose (rapid acting insulin)
Split-mixed- pre-breakfast dose (NPH)
143
Bedtime BG value is caused by what?
Meal- Dinner
Insulin-
Basal-bolus- Pre-dinner insulin (rapid acting)
Split mixed- (Pre-dinner insulin (rapid acting)
144
How does physical activity affect insulin?
Causes hyperglycemia due to "fight or flight" response caused by NE or EPI
Causes hypoglycemia due to the overexpression of the GLUT1 (insulin dependent) receptor. This increases the sensitivity of this receptor for 7-11 hours postexercise.
145
Recommendations to decrease risk of hypoglycemia with exercise
```
Make sure preexercise BG is >100mg/dL
Increase food intake
Reduce prandial insulin
Reduce overnight basal insulin
SMBG PRN
Simple carbs
```
146
Potential risks of hyperglycemia
```
Underestimating carb intake
High fat meal
Missed/inadequate medication doses
Ineffective insulin
Poor administration technique
Overuse of injection site
Less than usual activity
medications
Illness, pain, stress
```
147
Potential causes of hypoglycemia
```
Irregular timing of medications
Incorrect medication dosing
Overestimation of carb intake
Skipping/delaying meals
More than usual activity
Decreased insulin needs (weight loss, increased physical activity)
```
148
Lipohypertrophy
Build up of fat tissues because of insulin administration.
Need to rotate injection sites
Patients with this might need to increase insulin doses due to insulin not being absorbed
149
Dawn phenomenon
When hormones are released in the mornings because they have different cycles. You need to check overnight insulin to determine if hypoglycemia is in?caused by the dawn phenomenon
150
Which injection site has the most rapid absorption of insulin?
Abdominal fat
151
Hybrid closed loop system
Medtronic and T:slim
CGM
insulin pump with tubing
152
Control-IQ technology
CGM with no tubing
153
Sick day management
```
Continue basal insulin at normal dose
If not eating:
D/C premeal insulin and cover hyperglycemia with rapid-acting insulin Q 4-6 hours
Stay hydrated
Monitor every 1-2 hours
Check ketones every 4 hours if BG>250
```
Call MD if vomiting and BG >500 or moderate urine ketones
154
Prediabetes recommendations
Intensive behavioral lifestyle intervention programs
Achieve and maintain 7% loss of initial body weight
Moderate intensity exercise to at least 150min/week
Annual monitoring
Metformin 850mg BID should be used if
BMI>35
Age <60
H/O GDM
155
Pharmacotherapy for T2DM
Metformin preferred
Consider initiating insulin therapy if newly diagnosed, symptomatic, A1C >10% and/or BG >300mg/dL
Consider initiating dual therapy in newly diagnosed pts if A1C is 1.5-2% above target
In most patients, GLP-1 RA are preferred over insulin
156
Youth-onset T2DM
3 approved drugs- insulin, metformin, liraglutide
| If insulin targets are not met with metformin +/- basal insulin in children over 10 add liraglutide
157
What do you give to T2DM patients who are on metformin and have ASCVD
GLP-1 RA with proven benefit (Liraglutide, Dulaglutide, Semaglutide)
OR
SGLT-2 inhibitor with CVD benefit (Empagliflozin, Canagliflozin)
```
If A1C still above target:
For patients on GLP-1 RA add SGLT2 inhibitor
Add Dpp-4 if not on GLP-RA
Basal insulin
TZD
SU
```
158
What do you glve to T2DM patients who are on metformin and have HF or CKD
SGLT2 with evidence if GFR adequate (Dapagliflozin, Canagliflozin, Empagliflozin)
OR
Only if SGLT2 cant be used give GLP1-RA with proven CV benefits (Liraglutide, Dulaglutide, Semaglutide)
```
If A1C still above target:
For patients on SGLT2 inhibitor consider GLP1 RA
Add Dpp-4 if not on GLP-RA
Basal insulin
SU
```
159
What do you give T2DM patients if cost is a major issue?
SU or TZD
160
What do you give T2DM patients who need to lose weight?
GLP1-RA or SGLT2
161
What do you give in T2DM patients who need to minimize hypoglycemia?
DPP4
GLP1-RA
SGLT2i
TZD
162
When do you add insulin to a T2DM patient?
If not meeting goals and already on GLP1-RA or GLP1-RA not tolerated add basal insulin
Start at 10IU/day or 0.1-0.2units/kg/day
163
How do you titrate basal insulin for T2DM?
Start at 10IU/day or 0.1-0.2units/kg/day
| 10-20% every 2-3 days
164
What do you do if T2DM patient is on basal insulin and not meeting goals?
Add prandial insulin
One dose with largest meal of day
Initiation- 4U a day or 10% of basal dose
Titrate by 1-2 IU or 10-15% twice weekly
165
What to do if A1C above target in T2DM patients and patient is on basal and prandial insulin correctly titrated
Stepwise additional injections of prandial insulins and potentially proceed to full basal-bolus insulin
Consider split mixed regimen
Consider twice daily premixed insulin
166
Critical point for basal insulin T2DM
0.5units/kg or higher we worry about over-basalization of increasing basal doses. So the increasing basal doses are not working as effectively and you might need them
167
Stress hyperglycemia
Illness can cause hyperglycemia by increasing stress hormones (cortisol and EPI)
Hyperglycemia can lead to organ failure, sepsis, and death
168
Hyperglycemia in hospitalized patients
Any BG >140mg/dL
BG levels that are consistently above this may require treatment
A1C >6.5% suggests that diabetes preceded hospitalization
169
Critically ill patients (ICU) with hyperglycemia
IV insulin when BG gets between 140-180mg/dL
Maintain a BG target of 140-180mg/dL
Never let BG get below 110
Insulin infusion protocols are highly recommended
170
Noncritically ill patients with hyperglycemia in hospital
Maintain BG target of 140-180mg/dL
| Scheduled SQ insulin that delivers basal, nutritional, and correction components recommended
171
Oral antihyperglycemics in the hospital
Limited data
Concerned because of long duration of action of agents, NPO, limited oral intake, and alternative nutrition therapies (TPN)
172
IV insulin dosing in hospital
Protocols in specific hospitals determine rate
| 1unit/mL in 0.9% NaCl
173
Basal-bolus regimen in hospitalized patients
Preferred method in non-ICU patients
1. ) Determine the basal dose (Take 2/3rd of the total dose given in the ICU)
2. ) Determine TDD (basal dose x2)
3. ) Bolus insulin dose. These patients are eating very little so give 10% of basal dose for each meal. This will increase as the patient starts eating more.
4. ) Correction scale measurement based off of patients CF.
174
Hypoglycemia triggers in hospitalized patients
```
Sudden reduction in corticosteroid dose
Altered ability to report symptoms
Reduced oral intake
Emesis
New NPO status
Inappropriate timing of insulin
Reduced infusion rate of dextrose
Unexpected interruption in TPN or parenteral infusions
```
175
Hypoglycemia protocol if patient can take PO
BG <70 stop insulin
If BG 50-70 start rule of 15
If <50- give 30 grams carbs
176
Hypoglycemia protocol is patient cannot take PO
If awake: D5W 25mL IV push
If not awake:D5W 50mL IV push
No IV access- glucagon 1mg IM
177
Inpatient glucose monitoring
Bedside POC method preferred
If receiving nutrition, check prior to any carbs
If not receiving nutrition check q 4-6 hrs
IV insulin- check every 30minutes- 2 hrs
178
Enteral nutrition
Tube feed
179
Parenteral nutrition
Through IV, TPN
180
Glucocorticoid induced hyperglycemia
Elevated PPG BG
| Glucocorticoids increase insulin resistance
181
Glucocorticoid induced hyperglycemia treatment
Once daily prednisone and insulin naive-
NPH 0.1unit/kg for every 10mg prednisone
Once daily prednisone and at home insulin-
Add weight based total to normal basal insulin dose
Twice daily prednisone or dexamethasone- long acting insulin
182
Does DKA or HHS have higher mortality?
HHS
183
Diabetic ketoacidosis
Typically type 1 DM
| Uncontrolled hyperglycemia causes increased ketone production which leads to a metabolic acidosis
184
Hyperosmolar hyperglycemic state
Typically Type 2 DM
| Severely high BG, dehydration, and hyperosmolality
185
Counterregulatory hormones in DKA and HHS
All are increased
DKA- absolute insulin deficiency
HHS- relative insulin deficiency
186
What is the most common precipitating factor for DKA?
Infection in known T1DM patients
| Newly diagnosed T1DM
187
Why do some women not take their insulin?
Hyperglycemia causes weight loss and insulin causes weight gain
188
Clinical presentation of DKA
polyuria, polydipsia, weight loss, N/V, abdominal pain, dehydration, weakness, mental status changes, poor skin turgor , Kussmaul respirations, tachycardia, hypotension
189
Kussmaul respirations
Pt has abnormal respirations because body is trying to blow off CO2
DKA
190
Diagnostic features of DKA
Elevation in total blood ketone concentration
Ketones in urine- acetoacetate and acetone
Ketones in blood stream- beta-hydroxybutyrate
191
MUDPILES
```
Anion-gap metabolic acidosis
Methanol toxicity
Uremia
DKA
Paraldehyde toxicity
Infection
Lactic acidosis
Ethylene glycol toxicity
Salicylate toxicity
```
192
Anion gap metabolic acidosis
Anything >10-12mEq/L
193
Why do you check amylase and lipase in anion gap metabolic acidosis?
They are raised if the cause is pancreatitis
194
```
DKA findings:
pH-
Sodium bicarb-
Urine ketone-
Serum ketone-
Serum osmolality-
Anion gap-
Mental status-
```
```
pH- <7.3 (more severe with lower pH)
Sodium bicarb- <18 (the lower the bicarb is the more severe)
Urine ketone-Positive
Serum ketone-Positive
Serum osmolality- Variable
Anion gap- >10-12
Mental status- Alert to coma in severe
```
195
```
HHS findings:
pH-
Sodium bicarb-
Urine ketone-
Serum ketone-
Serum osmolality-
Anion gap-
Mental status-
```
```
pH- >7. 3 (more normal)
Sodium bicarb- Normal (>18)
Urine ketone- Small to none
Serum ketone- Small to none
Serum osmolality- >320mOsm/kg
Anion gap- Variable
Mental status-Stupor/coma
```
196
Treatment goals of DKA and HHS
Correct dehydration, hyperglycemia, and electrolyte imbalances
Treat with fluids, insulin (treating acidosis!), and electrolytes
197
Fluid therapy for treatment of DKA
Give 1-1.5 L in first hour 0.9% NaCl bolus immediately while waiting on labs.
If corrected Na normal or elevated- 0.45% NaCl at at rate of 250-500mL/hr
If corrected Na low- 0.9% NaCl at a rate of 250-500mL/hr
198
When do you want to see correction in DKA?
Fluid deficit- w/in 24 hours
Hyperglycemia- w/in 6 hours
Ketoacidosis- w/in 12 hours (this is why you continue giving insulin past when the hyperglycemia is fixed)
199
DKA dosing insulin therapy
Regular insulin
0.1units/kg bolus followed by a 0.1unit/kg/hour infusion
OR
0.14units/kg/hr infusion
You are not titrating insulin
Goal is to not drop glucose too quickly
200
When do you reduce rate of insulin therapy in DKA?
When BG is 200mg/dL you reduce rate to 0.02-0.05units/kg/hr and give D5W
Goal BG 150-200mg/dL until resolution of DKA
201
When do you give K with DKA?
If K <3.3
-Hold insulin and give K 20-30mEq/L until K >3.3
If K 3.3-5.2
-20-30mEq K/L of replacement fluid with insulin
If K > 5.2
Do not add K
Check serum K in 2 hours
202
When do you give bicarb in DKA?
When pH <6.9 give 100mEq bicarb
203
Criteria for resolution of DKA
```
BG <200mg/dL
Two of the following:
Serum bicarb >15mEq/L
Venous pH >7.3
AG <12
```
204
Criteria for resolution of HHA
Normal osmolality
| Normal mental status
205
Transition to SQ insulin after DKA
Make sure there is an overlap of 1-2 hours between discontinuation of insulin infusion and administration of SQ insulin
206
Complications of treating DKA
Hypokalemia
Hypoglycemia (BG monitoring q 1-2h)
Hyperchloremia
Cerebral edema
207
HHS causes
Typically in older adults due to restricted water intake.
| It involves over days to weeks
208
Energy balance
Energy intake- total energy expenditure
209
TEE
resting metabolic rate (RMR) x physical activity level (PAL)
210
Physical activity level
Sedentary- 1.2
Low to moderate- 1.4
Active- 1.6
211
Carbohydrates
4 calories/gram
| 45-65% total calories
212
Simple sugars
Fructose, fruits, milk (lactose)
| Less than 10% calories/day added sugars
213
Complex starches
Beans, peas, nuts, grains, starchy vegetables
214
Complex fiber
Insoluble- helps maintain a healthy digestive system and regularity
Soluble- Helps control BG and cholesterol
14 grams of fiber for every 1,000 calories
215
Protein
4 calories/gram
10-35% of total calories
0.8grams /kg/day of protein
Animal sources, plant s (soy, beans, nuts, quinoa
216
Fat
9 calories/gram\
| 20-35% of total calories from fat
217
Monounsaturated fatty acids
Healthy
| Avocadoes, nuts, seeds, olive oil, canola oil, peanut oil
218
Polyunsaturated fatty acids
Healthy
| ALA, soy beans, walnuts, flax seeds, DHA/EPA, salmon and other seafood
219
Trans fatty acids
margarines and processed foods
| Unhealthy
220
Saturated fatty acids
Unhealthy
Animal fat, coconut oil, palm oil, cocoa oil
Less than 10% of calories should come from fats
221
Daily sodium recommendations
Less than 2300mg/day
222
Alcohol
7 calories/gram
| Up to 2 drinks for men and 1 for women per day
223
Healthy eating plate
1/2 fruits and veggies
1/4 whole grains
1/4 healthy protein
skip sugary drinks
224
Starches grams of carbohydrate per serving
15
225
Fruits grams of carbohydrate per serving
15
226
Milk grams of carbohydrate per serving
12
227
Nonstarchy veggies grams of carbohydrate per serving
5
228
Meat, proteins, and fats grams of carbohydrate per serving
0
229
Women carb requirements
Need about 45-60 grams carbs at each of 3 meals and 15 grams for snacks prn
230
Men carb requirements
Need 60-75 grams carbs at each 3 meals and 15-30 grams carbs for snacks prn
231
Is there an ideal percentage of calories from carbs, proteins, and fat for people at risk for diabetes?
No
232
ADA total dietary allowance of carbs for adults w/o diabetes
130g/day to fulfill brains requirement
233
Two systematic reviews of the literature regarding GI and GL in individuals with diabetes report
No A1C impact
234
Does the ADA support limiting carbs for the general population?
No
235
Healthcare providers should focus on:
Emphasize nonstarchy veggies
Minimize sugars and refined grains
Choose whole foods over highly processed foods
Reduce carbs in pts with DM
236
Weight management
In T2DM, 5% weight loss is recommended. Optimal outcomes are seen at 15% or more weight loss if feasible
237
Diabetes remission
Maintenance of euglycemia or prediabetes level of glycemia with no meds for 1 year
238
Excess alcohol consumption can lead to
Hyperglycemia
| Alcohol in people with DM can inhibit gluconeogenesis and cause hypoglycemia
239
Etiology of obesity
Imbalance between energy intake and energy expenditure over time
240
Medications associated with weight gain
```
Anticonvulsants/mood stabilizers
Antidepressants
Beta blockers
antidiabetics
Atypical antipsychotics
Antihistamines
Corticosteroids
Hormonal contraceptives
```
241
Leptin
Comes from fat cells and decreases appetite.
| There is a leptin resistance in obesity.
242
What does an increase in FFA cause?
An increase in insulin
| -weight gain and insulin resistance
243
Defining obesity
A state of excess body fat as determined by measures in adiposity
BMI is used but does not take into account fat free mass
Can take intraabdominal fat waist circumference
244
BMI calculation
Weight in kg/height in m^2
245
Normal BMI
18.5-24.9 kg/m^2
246
Obesity BMI
>30 kg/m^2
247
Measuring waste circumference
Narrowest circumference in area between last rib and top of iliac crest
High risk
men >40
women >35
248
Weight loss goals
Initial goal: 5-10% loss of baseline weight w/in 6 months
Create an energy deficit of 500-750kcal/day
Women- 1200-1500 kcal/day
Men- 1500-1800 kcal/day
249
When would you consider medications in obesity?
BMI >30
| BMI> 27 with at least 1 associated obesity related condition
250
When would you consider metabolic surgery in obesity?
BMI >40
| BMI >35 with obesity associated comorbid conditions
251
When do you D/C medication for obesity?
In pregnancy
| If the response is less than 5% after 3 months
252
Phentermine
Approved for short term use
Controlled substance
MOA- NE releasing agent
Contraindications- anxiety disorders, heart disease, HTN, seizures, MAOI, pregnancy/breast feeding, hyperthyroidism, glaucoma, drug abuse, idiosyncrasy to symathomimetic amines
253
Orlistat
Chronic use
Alli- OTC
Xencal- Rx
Pancreatic and gastric lipase inhibitor
Contraindications- chronic malabsorption syndrome, cholestasis, oxalate nephrolithiasis, pregnancy/breastfeeding
254
Phentermine/Topiramate
Dose titration
MOA- GABA receptor modulation plus NE releasing
Chronic
255
Naltrexone/Bupropion
BBW- suicidal ideation
Goal dose 2 tablets BID 32/360mg
Chronic
Reuptake inhibitor of Ne and dopamine; opioid antagonist
256
Saxenda
Liraglutide
Chronic
GLP1 RA
257
Metabolic surgery
Achieves superior glucose control and reduction in CV risk factors in obese patients with T2DM
258
Metabolic surgery RYGB
Gastric bypass
| Most favorable risk-benefit ratio
259
Metabolic surgery VSG
30% of procedures
Excellent weight loss
Long term studies needed
260
Metabolic surgery LAGB
19% of procedures
| Greater risk of complications
261
Metabolic surgery BPD-DS
2% of procedures
Most effective but least favorable risk-benefit profle
Consider if BMI >60
